Acylation process

Abstract

The present invention is concerned with the acylation of indoles, specifically the preparation of 3-acylated indoles which may be further treated to provide indoles having an alternative substituent at the 3-position.

1. A process for the preparation of a compound of formula (III) 
                 
 which comprises as a first step, separately and simultaneously adding to a stirred solution of an indole of formula (II) 
                 
 
 (i) a solution containing an acid chloride of formula 
                 
 
 (ii) a solution containing an alkyl or aryl magnesium halide in such a way that  
 (a) the solutions (i) and (ii) are added with sufficient separation to prevent their reacting with one another; and  
 (b) the solutions (i) and (ii) are added at equivalent rates of molar addition and as a second step, reducing the product.  
 
     
     
       2. A process according to  claim 1  wherein the magnesium halide is an alkyl or aryl magnesium bromide. 
     
     
       3. A process according to  claim 1  wherein the magnesium halide is ethyl magnesium bromide. 
     
     
       4. A process according to  claim 1  wherein said reduction is carried out using lithium aluminum hyride in tetrahydrofuran. 
     
     
       5. A process according to  claim 1  wherein the compound of formula (III) so obtained is reacted with phenylvinylsulfone in the presence of an organometallic catalyst to provide a compound of formula (IV): 
                 
 
     
     
       6. A process according to  claim 5  wherein the compound of formula (IV) so obtained is subsequently converted by catalytic hydrogenation to a compound of formula